title: Pre- and perinatal hypoxia associated with hippocampus/amygdala volume in bipolar disorder.
abstract: BACKGROUND
  Pre- and perinatal adversities may increase the risk for schizophrenia and bipolar disorder. Hypoxia-related obstetric complications (OCs) are associated with brain anatomical abnormalities in schizophrenia, but their association with brain anatomy variation in bipolar disorder is unknown.
  
  
  METHODS
  Magnetic resonance imaging brain scans, clinical examinations and data from the Medical Birth Registry of Norway were obtained for 219 adults, including 79 patients with a DSM-IV diagnosis of bipolar disorder (age 29.4 years, s.d. = 11.8 years, 39% male) and 140 healthy controls (age 30.8 years, s.d. = 12.0 years, 53% male). Severe hypoxia-related OCs throughout pregnancy/birth and perinatal asphyxia were each studied in relation to a priori selected brain volumes (hippocampus, lateral ventricles and amygdala, obtained with FreeSurfer), using linear regression models covarying for age, sex, medication use and intracranial volume. Multiple comparison adjustment was applied.
  
  
  RESULTS
  Perinatal asphyxia was associated with smaller left amygdala volume (t = -2.59, p = 0.012) in bipolar disorder patients, but not in healthy controls. Patients with psychotic bipolar disorder showed distinct associations between perinatal asphyxia and smaller left amygdala volume (t = -2.69, p = 0.010), whereas patients with non-psychotic bipolar disorder showed smaller right hippocampal volumes related to both perinatal asphyxia (t = -2.60, p = 0.015) and severe OCs (t = -3.25, p = 0.003). No associations between asphyxia or severe OCs and the lateral ventricles were found.
  
  
  CONCLUSIONS
  Pre- and perinatal hypoxia-related OCs are related to brain morphometry in bipolar disorder in adulthood, with specific patterns in patients with psychotic versus non-psychotic illness.
authors.affiliation: Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: U K
authors.initials: UK
authors.lastname: Haukvik
authors.affiliation: Department of Psychiatric Epidemiology, Lund University, Lund, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: McNeil
authors.affiliation: Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: E H
authors.initials: EH
authors.lastname: Lange
authors.affiliation: K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Melle
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: O A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Agartz
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000473:pathology*; D001238:Asphyxia Neonatorum / Q000453:epidemiology / Q000473:pathology*; D001714:Bipolar Disorder / Q000453:epidemiology / Q000473:pathology*; D015897:Comorbidity; D005260:Female; D005311:Fetal Hypoxia / Q000453:epidemiology / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009664:Norway / Q000453:epidemiology; D012042:Registries / Q000706:statistics & numerical data*; D055815:Young Adult